For patients who have had COVID-19 for a long time, exercise can worsen symptoms, a condition called “post-exercise fatigue.” New research reveals what's going on in their muscles.
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For patients who have had COVID-19 for a long time, exercise can worsen symptoms, a condition called “post-exercise fatigue.” New research reveals what's going on in their muscles.
Eric Isaacson/Getty Images/Tetra Images RF
Let's go to the gym. Please get back in shape.
This is what many long-term COVID-19 patients say when they talk about the severe fatigue that comes with even mild physical activity.
These symptoms of fatigue, or feeling tired after exercise So-called, this is a feature of long-term coronavirus and similar complex illnesses such as chronic fatigue syndrome and ME/CFS.
The idea that exercise helps patients has proven difficult to shake, despite evidence suggesting that it is not simply a case of deconditioning that patients can overcome by working through their pain.
“I don't think the message was strong enough,” he says. David Putrino, Director of Rehabilitation Innovation at Mount Sinai Health System. “It's clear that this is not a typical response to exercise.”
Research results were published this month nature communications give new weight to this evaluation.
By taking biopsies before and after exercise from patients with long-term COVID-19 infection, Dutch scientists have discovered widespread abnormalities in muscle tissue that may explain this severe response to physical activity. You've built an amazing picture.
One of the most surprising discoveries is that mobile phone power plants mitochondriathe tissue is starved of energy.
“We saw this right away, and it's very profound,” he says. braeden charltonone of the study authors from Vrije University in Amsterdam.
Tissue samples from long-term coronavirus patients also revealed severe muscle damage, impaired immune responses, and the accumulation of microcoagulation.
“This is a very real disease,” Charlton said. “We see this in basically every parameter we measure.”
Exercise test reveals abnormality in cellular energy system
Most people experience delayed onset muscle soreness after an intense workout, but post-exercise fatigue is completely different.
“It's not just the pain,” Charlton said. “For many people, it can be completely debilitating for days or weeks.”
Symptoms vary, but the most common trends include muscle pain, increased fatigue, and cognitive impairment, usually referred to as “brain fog,” which lasts for about a week after exercise.
the studyResearchers based at Vrije and the Amsterdam UMC Health Center compared 25 patients with long-term COVID-19 infection to healthy controls who had fully recovered from COVID-19 and had no persistent symptoms. did. Both groups were asked to exercise for approximately 10 to 15 minutes on a stationary bike until their aerobic capacity gradually reached its maximum.
The researchers drew blood multiple times, one week before and one day after exercise, and took two muscle biopsies from the thigh.
“Their baseline was already compromised, and maximal exercise caused their baseline to drop even more,” Charlton says.
as seen in Other long-term coronavirus studies, the problem had nothing to do with lung or heart function. Instead, something was making it difficult for the muscles to take in oxygen from the blood.
Using a technique called respiration measurementDutch researchers found evidence of over-oxygenating muscle tissue and mitochondria not functioning properly
Further testing reveals more clues
Metabolites in the blood related to energy production were also significantly reduced in patients with long-term COVID-19 infection. And they started producing lactic acid, the cell's “last resort” fuel, much faster than healthy people during exercise, a sign that the cell's energy system is malfunctioning. That's one sign.
“Mitochondrial function is significantly reduced compared to healthy people,” Charlton says.
Taken together, the researchers say the results support the hypothesis that mitochondrial dysfunction plays a role in long-term coronavirus symptoms, such as fatigue and post-exercise malaise. Dr. David Systroma physician at Harvard Medical School and Brigham and Women's Hospital.
“They were able to link the symptoms to these organic changes,” he says. “I was impressed with that.”
In his research, Systrom found evidence of abnormal oxygen uptake by skeletal muscles during peak exercise in both long-term COVID-19 patients and ME/CFS patients. This indicates a problem with the oxygen supply to the mitochondria.
Meanwhile, the Dutch study suggests there may be an “intrinsic dysfunction” in mitochondria's ability to generate energy, he says.
Systrom said both may be happening in patients with long-term COVID-19 infections. “There may be two ends of that spectrum,” he says. “That's something that future studies really need to look at.”
Biopsy shows clear signs of muscle damage
The story doesn't end with mitochondria.
A muscle biopsy taken after the exercise test revealed other troubling events.
“You end up sustaining much more muscle damage than a healthy person,” Charlton says. “And their maximum capacity is also lower, so the damage occurs at an earlier point.. ”
A closer look at muscle tissue showed that patients with long-term coronavirus infection had greater atrophy (shrinking of fibers) than healthy controls. There was also a “huge amount” of cell death, or “necrosis,” which occurs when immune cells infiltrate and break down tissue, he said.
This data suggests some sort of altered immune response to exercise in post-exercise fatigue.
“It's not just about muscle function, it's about how the immune system receives exercise signals,” Charlton says.
He said the tissue-level analysis of muscle defects was “shocking” and could help explain the pain, fatigue and weakness patients experience. Akiko Iwasaki He was a professor of immunobiology at Yale University but was not involved in the research.
An additional finding that T cells, part of the immune system's arsenal, were infiltrating the muscles of patients with long-term COVID-19 infections also caught Iwasaki's attention, possibly leading to an “autoimmune reaction within muscle cells.” It is thought that this indicates that
“In healthy muscle, very few, if any, T cells are found,” she says.
Microcoagulation is a sign of major blood vessel problems
Digging deep into the muscle tissue also revealed another increasingly familiar feature of long-term coronavirus pathology: microcoagulation.
Researchers found these were significantly elevated in people with symptoms. This feature only worsened after exercise.
The South African researchers zeroed in on these microclots, which carry “trapped inflammatory molecules”, as an indication of damage to a patient's vasculature.
The Dutch study found no evidence that microthrombi block small blood vessels, one of the hypotheses. Instead, they remained within the organization.
The implications of this discovery are potentially very large. Lesia Pretoriusa professor of physiological sciences at Stellenbosch University in South Africa, was not involved in the study.
“That means the microcoagulation may actually have traveled through the damaged vasculature to reach the muscle,” she says. “What is frightening, but perhaps very important, is that this may be happening in other organizations as well.”
In this scenario, microcoagulation may reflect the degree of damage to the blood vessel lining, which may also impair oxygen delivery to muscle tissue.
Pretorius said that if the vasculature was “totally destroyed”, “mitochondria would be severely affected”, but further research was needed before making any final conclusions.
The root cause of the prolonged spread of the new coronavirus remains unknown. However, one leading theory is that ongoing chronic infection may be causing downstream effects.
Researchers investigated this hypothesis. Researchers found evidence of viral proteins from SARS-CoV-2 in muscle tissue, but found no differences between the long-term coronavirus infection group and the control group, which were It was concluded that it was a residual substance and did not necessarily cause post-exercise fatigue.
Experts warn exercise can be 'harmful' and other approaches are needed
The role of exercise in treating post-exercise fatigue remains “highly controversial,” said Systrom of Harvard University, who studies exercise in the context of other complex chronic diseases such as ME/CFS. says.
“Post-exercise fatigue is a characteristic symptom of these diseases and not a characteristic of deconditioning,” he says. “We can't simply ask these patients to go to the gym and solve their problems.”
Long COVID itself is an umbrella term that includes a wide range of symptoms that can have different underlying causes.
Systrom says some of these patients may benefit more than others from gradual exercise, especially after medical treatment is first established.
In his study, Charlton said he looked at other studies to make sure what he observed was not due to physical inactivity. He also noted that the registered long-term coronavirus patients were not bedridden and took an average of 4,000 steps a day.
Mount Sinai's Professor Putrino said the study is a much-needed wake-up call for the wider medical field, and that the biology of the energy crash and onslaught of symptoms experienced by patients with long-term COVID-19 and similar conditions. We believe this is clear evidence of scientific basis.
“Contrary to what patients have been sold over the past few decades, symptoms such as extreme fatigue and fatigue on exertion are psychological or physical conditioning issues,” he says. “Physical exercise has a negative impact on the bodies of people with these diseases.”
His general advice is to avoid exercising if you feel tired after exercise and instead practice “energy conservation.”
At the clinic, Putrino said,Autonomic nerve rehabilitation“For these patients.
The purpose of exercise is to improve cardiovascular health, which he may recommend for patients recovering from severe pneumonia, but this type of rehabilitation requires much lower intensity and duration. Post-exercise fatigue is also taken into account.
“We need to move away from the misconception that no pain means no gain,” he says.
